Prostate specific antigen (PSA) is a prostatic enzyme with biological significance. As a proteolytic enzyme, it cleaves seminal coagulum proteins to release sperm for fertilization. It has been implicated in infertility because men with highly viscous semen have abnormal sperm motility and are often infertile. It may also regulate cellular growth by cleaving insulin growth factor-binding proteins (IGFBP's), thereby releasing insulin growth factor (IGF) into the circulation. There is recent evidence that prostate cancer increases the level of the active form of PSA before it is inactivated by alpha-1-antichymotrypsin. The precursor form (zymogen or pro-PSA) as predicted by the cDNA requires proteolytic activation. If we can discover how pro-PSA is activated, we may elucidate the specific events affecting the level of PSA enzyme activity in disease stated. In order to understand how the pro-PSA is activated by a prostate-specific enzyme, and to test the hypothesis that the expression and/or activity of this putative activator may be altered in certain disease states, we propose to: 1. Isolate and characterize the activator of pro-PSA from prostate tissue by utilizing recombinant pro-PSA as the substrate. 2. Clone and express the pro-PSA activator. 3. Test a candidate activator: hGK-1, a prostate-specific serine protease. 4. Analyze the level of the pro-PSA activator in various disease states by immunohistochemistry.